Mapping The Microbial Make-Up Of Healthy Humans

There are trillions of germs that live on us. What are they? What do they do? Inquiring minds want to know, and so they set to find out. And after five years of research, a group of several hundred scientists has released a census of the bacteria, viruses, fungi, other microorganisms that call our bodies home.

The sequenced the genetic microbes of the mouth and nose, the skin, the gut, other areas of the body, and the diversity, variety and function of these microbes populating the human body surprised them. Their research papers were published in Nature, Nature Methods and several Public Library of Science publications.

Dr. Curtis Huttenhower is assistant professor in the Department of Biostatistics at Harvard School of Public Health. He helped coordinate the Human Microbiome Project Consortium, and that's the analysis paper in Nature, and was co-author of two other related papers. He joins us from Cambridge, Massachusetts. Welcome to SCIENCE FRIDAY.

CURTIS HUTTENHOWER: Excellent, thanks so much, Ira. It's good to be here representing the consortium.

FLATOW: Thank you. I mean, how many, how many microorganisms inhabit our body?

HUTTENHOWER: Lots.

(LAUGHTER)

HUTTENHOWER: The rule of thumb is that each of us carries around about 10 times as many microbial cells as human cells and that they have about 100 times as many genes as we do. So not only are we outnumbered, we're outgunned. They're able to perform a lot of biological functionality that we don't get to do, necessarily, in our own genome.

FLATOW: So is this really the first census of figuring out who they are and what they do?

HUTTENHOWER: This has been the largest and deepest survey of this many healthy individuals over this many different body sites. It's been interesting since each of these body sites, these areas, represent really a different ecosystem. They're very different. So profiling what the normal variation, even in health, there's a tremendous number of differences between people and seeing how those map out, what the boundaries of that healthy variation are from person to person at each of these different body sites is really important for the project to lay out.

FLATOW: So which site has the most germs in it?

HUTTENHOWER: Well, it depends by what you mean by most. An example might be in the oral cavity. We observe the largest diversity there, for example the greatest difference in the number of bugs that tend to be in the mouth and how they differ in abundance. But when you go looking between individuals, a lot of that diversity is shared, whereas if you go to a sparser ecosystem - the skin has been called, for example, a microbial desert.

Each person tends to carry fewer bugs on the skin, but those fewer bugs are more different between people. So there's lots of ways to slice this variation that we tried to look at in these papers.

FLATOW: And which part of the body would we say has the fewest number?

HUTTENHOWER: The fewest number, the skin for example is a good example of a habitat that tends to carry fewer microbes.

FLATOW: Our number is 1-800-989-8255. We're talking with Curtis Huttenhower about the microbes in our bodies, interesting topic if you want to get involved. We're going to talk about where they are, what they do and how fascinating they are. Our number, 1-800-989-8255. You can tweet us, yes, @scifri, @-S-C-I-F-R-I, or go to our website at sciencefriday.com or Facebook. We'll be back after this break, so stay with us. I'm Ira Flatow.

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FLATOW: This is SCIENCE FRIDAY; I'm Ira Flatow. We're talking with Dr. Curtis Huttenhower, who is - coordinated the Human Microbiome Project Consortium. They put papers in Nature and other places talking about all the bacteria, the germs, the viruses, the fungi that live, grow, thrive in our bodies, how many there are and how many - where they live.

Dr. Huttenhower, it's interesting for me to hear you say that the skin is relatively a desert because we've had other scientists on who do nothing but swab people's skins down and look at the biota that's growing on them. They find countless numbers. Is this a comparative number, you're saying, that compared to other parts of the body, the skin is like a desert?

HUTTENHOWER: Absolutely, and if you think about macro ecosystems, for example, it's certainly not true that you find no life in a desert. But if you compare that, for example, to nutrient availability for these bugs in the mouth or in the gut, there are differences both in energy metabolism and what's available for the bugs to eat and in the ways they interact with each other and with your immune system, for example.

There's a great deal more surface area in your gut, exposing all of these microbes to your immune system than there would be on the skin.

FLATOW: So why doesn't the immune system, if there are trillions of these bugs in our guts, why don't the immune system attack it?

HUTTENHOWER: That's an excellent question. That's something that's been under a lot of scrutiny lately since there are at least two answers, one having to do with sort of historical co-evolution. There have been several other good studies that look at how different hosts, other mammals, for example, have co-evolved with their microbiomes.

And then for humans in particular, it's thought that we experience, early in life, training of the immune system based on the microbes that are present. So studies are looking at, for example, the effect of different exposures or antibiotics early in life that might interfere with that training.

FLATOW: You said there was a difference between - not only between the bugs that inhabit our own bodies but between me and someone else. We have different microbiota...

HUTTENHOWER: Definitely. One of the things to keep in mind when thinking about the diversity in the microbiome is that even though people share 99-percent-plus of their human DNA, of our genomes, we're lucky if we share 50 percent of our microbiome at any one particular body site. So understanding all of that variation and defining its boundaries made that part of the project's goal very important.

VICTORIA: Hi, thanks for taking my call. I was wondering whether or not your researcher was able to separate his sample people into C-sections versus vaginal birth, due to the colonization effect of birth.

HUTTENHOWER: So that's an area where there have been some good studies on the differences that show up in infants' microbiomes soon after birth, depending on whether they're delivered naturally or by C-section. This study looks specifically at adults, 18 to 40. So we had a little bit of information available about their early life experiences, but we didn't go looking for factors that would be more specific to infancy and development.

FLATOW: What about pregnant women and non-pregnant women?

HUTTENHOWER: We have to be very careful when we say this is a study about health. It's more about a baseline or reference study, since pregnancy was specifically - excuse me, excluded from the population.

FLATOW: Thank you, Victoria, good question.

VICTORIA: Thank you.

FLATOW: So women who were - so you didn't study whether the biome changes if you're pregnant or before or after you get pregnant or other parts of the body that are involved, might be.

HUTTENHOWER: There were some other studies elsewhere in the consortium and ongoing now using this as a baseline with which to compare, for example, the pregnant microbiome. But this was - one of the defining characteristics of the Human Microbiome Project in particular was the very high stringency of clinical health screening at all of the body sites that the subjects had to meet.

FLATOW: You mentioned or at least in your paper and in other studies the difference that just a few centimeters can make. And I'm thinking about the gumline here, above and below the gumline.

HUTTENHOWER: That's a great example. There are more differences between these 18 different body sites than there are between individuals, even within a body site, and I've already said how big differences between the individuals are. And that was true even for these very similar microbial habitats like the two surfaces just above and below the gumline, that even though those communities were - overall they shared a lot of similarities, you could still find differences within individuals just across those few millimeters due to, for example, there's more oxygen availability.

FLATOW: So you mean the type or the number of bacteria that would be above and below the gumline?

HUTTENHOWER: Mostly type, mostly type.

FLATOW: And what kind of type inhabit our guts? Do we all have the same bacteria that digest food? We know we need bacteria to digest food. Do we all have the same colonies?

HUTTENHOWER: That's - like all of the other habitats, there is a wide range of variation in the gut, even at the level of whole groups of bacteria, that certain individuals would be populated by one large group of bacteria, whereas other individuals, again even with this relative homogeneous, healthy population, would have a completely different group of bacteria.

But one of the things we did find during this study is that the same tasks have to get carried out. Even when you have different bugs in a habitat like the gut, they still have to be performing the same jobs. So it's interesting to see how these ecosystems found a balance of getting the necessary jobs performed, the necessary microbial processes, even when it was by different bugs in different people.

MICHAEL: Yeah, I was wondering, because of the sheer number of microbes on the body, why don't we notice? I mean, what's the volume? Like if I weigh 200 pounds, how much of that weight is actually microbes? And are they all bacteria, or are you counting viruses and fungus, too? And I was just wondering about that stuff.

And then one other question: Do you think these things are teaming up and causing some kind of toxins that could be maybe be causing cancer and other diseases?

FLATOW: All right, thanks for calling, Michael. Yeah, how much do they weigh?

HUTTENHOWER: More than you probably want to think about. Another good rule of thumb there is it's about two to five pounds per adult. So even though there are many more microbial cells, they're small, but small is non-trivial. It's still several pounds of microbes, mostly in your gut.

As far as their roles in disease, that was one of the plans of this project looking ahead. The HMP, even though it studied or because it studied a healthy cohort, now gives us the boundaries of what the range of normal looks like so that if we look at new populations, either in different locations or with different genetic backgrounds or in specific diseases, we'll be better able to define which microbes or which microbial processes fall outside of those bounds in disease conditions of interest.

FLATOW: You mentioned the skin being one of the least populated areas. Also from your study, it seems that the vaginal area was the least populated, too, correct?

HUTTENHOWER: It tended to be very low diversity and very structured, in a way. There are few discrete configurations that the vaginal community tends to take on in health, mostly characterized by a majority of just a few bugs.

FLATOW: Here's a tweet that came in from Dustin Bowers(ph). It says: What does - what do you think about the difference between smokers and non-smokers? Is there any change in the diversity?

HUTTENHOWER: That's a great question. That was another condition that was excluded based on the health criteria in this particular study, but it is of current interest in conditions like inflammatory bowel disease. So a lot of autoimmune conditions in that family are thought to have a big component in the microbiome because it has such a large interaction with our immune system and to have previously been linked to smoking as an exposure, for example. So that's separate work that's ongoing now.

FLATOW: Phil(ph) in Berkeley, hi, welcome to SCIENCE FRIDAY.

PHIL: Hi, thank you.

FLATOW: Hi there.

PHIL: Hello? My question is this: Where are we talking - what location are we talking about? Are we talking about internal organs that don't have any access to the outside? Are we talking the bloodstream? Are we talking like the liver, the pancreas? Where exactly - or the brain or like all those places that are not supposed to be having any kind of access to the outside? Where exactly are we talking about, and what organs?

HUTTENHOWER: So at any place you can put a Q-Tip. So internal organs, for example, don't tend to have this sort of microbial exposure. There are conditions under which there can be circulating bacteria or viruses in the blood, but that typically does not occur in health, especially.

FLATOW: Some of those Q-Tips would be pretty long, wouldn't they?

(LAUGHTER)

HUTTENHOWER: Don't ask us too much about the sampling for the project.

(LAUGHTER)

FLATOW: Why not? How did - I'm going to ask it because you said no. How did you sample them?

HUTTENHOWER: So a lot of it was swabbing, for example, swabbing the inside of the cheek or the skin. Subjects did provide a self-collected stool sample to represent the gut community, and that's, you know, probably one of the trickier parts of helping the volunteers through the study. So these were very generous, very supportive volunteers who put up with all this work in the name of science.

FLATOW: So it's not somebody maybe while you're getting a colonoscopy or something, you say, hey, Doc, would you get me a sample while you're in there?

HUTTENHOWER: Not for this. There are microbiome studies, for example, for inflammatory bowel disease where that's possible,, but not in this case.

FLATOW: And what was the biggest surprise (unintelligible) study this? What was more surprising about your findings?

HUTTENHOWER: I was a personal fan of the degree to which the core microbiome, the similarities were represented by the kinds of shared jobs that I mentioned earlier. That was a finding that I enjoyed from the project. Another really interesting one was the degree to which this variation is personalized. So it's not just that everyone has big differences, and there are groups of microbes that even when people carry very similar bugs or, quote, the same bug, those, quote, same bugs can have small variations in their genomes just like we do between people, so that everyone is a snowflake with respect to the microbiome.

FLATOW: Do we change over time? Our microbiomes, does it sort of evolve or move or shift like a colony of anything else would?

HUTTENHOWER: There are definitely changes. We took up to three time points in this study to look more at stability than really temporal change, since that's - that would take more than three samples. And individuals were relatively stable, but there are certainly more than - quite a bit more than no change over time.

FLATOW: Let's go to Henry in Athens, Ohio. Hi, Henry.

BOB HENRY: Oh, it's Bob Henry. Hi. How are you, gentlemen?

FLATOW: Hi there.

HENRY: I have a quick question, and I'll take my answer off the air. If a person were to be born in a sterile environment, would survival be possible? And I'll take my answer off the air.

FLATOW: OK. Thanks. Where would they get their biome from if they were in a sterile environment?

HUTTENHOWER: So for people, we don't really know the answer to that, but it is fairly commonly done for mice as a model system for the microbiome. And they're definitely a little broken. Training the immune system, for example, is an important part of what happens from the microbiome soon after birth, but they're not - they are viable. So it's not, at least in mice, a lethal condition, but it's not a healthy condition either.

FLATOW: Talking with Dr. Curtis Huttenhower on SCIENCE FRIDAY from NPR. Interesting tweet came in from Melody Slickman(ph), who says meat eaters versus vegetarian. Any change in the biome between the two?

HUTTENHOWER: Very good question, something I'm personally interested in as a vegetarian. In this particular study, we took healthy volunteers, and we did look at their diets afterwards and actually didn't have enough vegetarians to be able to determine differences here. But that's something that we've been, again, looking at elsewhere now that we have this baseline against which to compare new studies.

FLATOW: Well, Dr. Huttenhower, that's what I would ask next. Where do you go from here? Do you expand this or what?

HUTTENHOWER: Absolutely. And this really is - inasmuch as much as this is a huge project, and in a way some of the most exciting work is yet to come because it gives us that map, it gives us a context in which we can now better understand new studies of the microbiome, particularly in disease. So...

FLATOW: Will it help us understand how to make better antibiotics possibly?

HUTTENHOWER: I would say targeted antibiotics are of a special interest, being able to disrupt just the bad guys without disrupting the good guys. And it's also expected to be a large component of personalized medicine. Just like our own genomes have become since the Human Genome Project, we'd like to be under - be able to understand individuals' microbiomes as a diagnostic, for example, for their disease risk or as a method by which we can start to treat disease in the future.

FLATOW: If you hang out with the same people, do you eventually wind up with the same microbiome, maybe in your family, your dormitory, anything like that?

HUTTENHOWER: It's a good question. It's also hard to study in people but has been observed to be the case in mice. So again, I know there are studies looking at exactly that now, since you can study that in humans.

FLATOW: What happens when you travel and you get tourists, you know, (unintelligible) or other disease going to another country? What's going on inside your body? Are you trying to replace your old microbiome with stuff from the other place you're visiting?

HUTTENHOWER: There's a lot that changes all at once with something like travel. So you're exposing yourself to different microbes. You're exposing yourself to different food. There's stress involved. So that's another condition that's thought to have a microbiome component, but the causality for that hasn't been pinned down just yet.

FLATOW: And here's a tweet coming in from Shaza(ph), who says: Could this have some role in understanding skin diseases like psoriasis?

HUTTENHOWER: Absolutely. So I - when I say that the skin is a desert, again, there's - it certainly doesn't mean that there aren't microbes there, and it doesn't mean that they don't interact with our immune system. That's thought to be one of the potential links to conditions like psoriasis or atopic dermatitis.

FLATOW: Let's get a quick last question in from Dan in Eugene, Oregon. Hi, Dan. Quickly.

DAN: Hi. Yeah. Is there any difference between - everything being normal otherwise - any difference in the ratio of these different microorganisms (unintelligible)...

FLATOW: Which are the most? Yeah, what kind of exactly different - can you name the different kinds of microbes you're talking about?

HUTTENHOWER: I see. So each body area represents sort of a major group of microbial ecologies, and just like macroecologies tend to be populated by a few dominant organisms, the same thing is true in the microbiome. So each of these - the five major areas that we looked at for these body sites tended to have a couple dominant bugs there. So, for example, the streptococci and the oral cavity, where different streptococci might be dominant in most individuals, or the bacteroides or members of the firmicutes in the gut were dominant in most people, varying from person to person.

FLATOW: Thank you very much, Dr. Huttenhower, for taking time to be with us today.

Excellent. Thanks again.

Good luck to you. Dr. Curtis Huttenhower is assistant professor in the Department of Biostatistics at Harvard Public School of - Harvard School of Public Health. He helped coordinate the Human Microbiome Project Consortium's analysis paper in Nature. We're going to take a break, but we're still going be talking about bugs and bacteria. There are some that wear armor. They have a suit of armor that looks just like chainmail, and we've seen it now for the first time. We'll tell you what it looks like after this break. So stay with us. We'll be right back. Transcript provided by NPR, Copyright National Public Radio.